Transdermal drug delivery apparatus and methods

ABSTRACT

A transdermal drug delivery apparatus includes a receptacle having a housing and a microneedle assembly mounted to the housing. The apparatus includes a reservoir for being mounted to the receptacle. The reservoir has an interior for containing fluid for being supplied to the microneedle assembly. The apparatus is adapted so that, when the apparatus is assembled, the reservoir is configured to move relative to the microneedle assembly along a path from an outer position to an inner position. The reservoir is closer to the microneedle assembly in the inner position than in the outer position. In the outer position, the reservoir is out of fluid communication with the microneedle assembly, and in the inner position, the reservoir is in fluid communication with the microneedle assembly. The apparatus also includes a plurality of connector parts spaced apart from one another along the path.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 15/305,193, filed on Oct. 19, 2016, the entirecontents of which are incorporated herein by reference. U.S. patentapplication Ser. No. 15/305,193 is the U.S. national stage applicationof International Application No. PCT/US2015/028150, filed on Apr. 29,2015, the entire contents of which are incorporated herein by reference.International Application No. PCT/US2015/028150 claims priority to U.S.Provisional Patent Application No. 61/996,149, filed on Apr. 30, 2014,the entire contents of which are incorporated herein by reference.

FIELD OF THE DISCLOSURE

The present subject matter relates generally to an apparatus fordelivering drug formulations to a patient through the skin utilizing amicroneedle assembly.

BACKGROUND

Numerous apparatus have previously been developed for the transdermaldelivery of drugs and other medicinal compounds utilizing microneedleassemblies. Microneedles have the advantage of causing less pain to thepatient as compared to larger conventional needles. In addition,conventional subcutaneous (often intra-muscular) delivery of drugs via aneedle acts to deliver large amounts of a drug at one time, therebyoften creating a spike in the bioavailability of the drug. For drugswith certain metabolic profiles this is not a significant problem.However, many drugs benefit from having a steady state concentration inthe patient's blood stream; a well-known example of such a drug isinsulin. Transdermal drug delivery apparatus are technically capable ofslowly administering drugs at a constant rate over an extended period oftime. Alternatively, transdermal drug delivery apparatus may administerdrugs at variable rates. Thus, transdermal drug delivery apparatus offerseveral advantages relative to conventional subcutaneous drug deliverymethods.

There is a desire for transdermal drug delivery apparatus that provide anew balance of properties.

SUMMARY

In one aspect, a transdermal drug delivery apparatus generally comprisesa receptacle comprising a housing and a microneedle assembly mounted tothe housing, a reservoir for being mounted to the receptacle, thereservoir having an interior for containing fluid for being supplied tothe microneedle assembly, and a plurality of connector parts. Theapparatus is adapted so that, when the apparatus is assembled, thereservoir is configured to move relative to the microneedle assemblyalong a path from an outer position to an inner position. The reservoiris closer to the microneedle assembly in the inner position than in theouter position. In the outer position, the reservoir is out of fluidcommunication with the microneedle assembly. In the inner position, thereservoir is in fluid communication with the microneedle assembly. Theplurality of connector parts are spaced apart from one another along thepath, and configured for releasably securing the reservoir in a firstposition, and securing the reservoir in a second position.

In another aspect, a method of at least partially using a transdermaldrug delivery apparatus is provided. The method generally comprisesfastening the apparatus to a user. The method further comprises engaginga microneedle assembly of the apparatus against skin of the user so thata first force provider of the apparatus forces the microneedle assemblyagainst the skin. While the apparatus is fastened to the user and thefirst force provider is forcing the microneedle assembly against theskin, the method also comprises causing a second force provider of theapparatus to at least indirectly force fluid to flow from a reservoir ofthe apparatus to the microneedle assembly.

In yet another aspect, a method of using a transdermal drug deliveryapparatus is provided. The method generally comprises engaging amicroneedle assembly of the apparatus against skin of a user, comprisingcausing relative movement between a housing of the apparatus and theuser. The method also comprises then moving a reservoir of the apparatusinto fluid communication with the microneedle assembly, comprisingmoving the reservoir relative to both the housing and the microneedleassembly. The moving of the reservoir is comprised of pushing a portionof the apparatus that is for moving the reservoir. The pushing of theportion is comprised of pushing the portion with sufficient force sothat at least one connector of the apparatus at least partially releasesthe portion from the housing in response to the pushing. The moving ofthe reservoir is responsive to the at least one connector of theapparatus at least partially releasing the portion from the housing.

The foregoing presents a simplified summary of some aspects of thisdisclosure in order to provide a basic understanding. The foregoingsummary is not extensive and is not intended to identify key or criticalelements of the invention or to delineate the scope of the invention.The purpose of the foregoing summary is to present some concepts of thisdisclosure in a simplified form as a prelude to the more detaileddescription that is presented later. For example, other aspects willbecome apparent from the following.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, reference is made to the accompanying drawings, whichare not necessarily drawn to scale and may be schematic. The drawingsare exemplary only, and should not be construed as limiting theinventions.

FIG. 1 is a pictorial view of a drug deliver apparatus in itspreactivated configuration and including a retention ring, in accordancewith a first embodiment of this disclosure.

FIG. 2 is a side elevation view of the drug delivery apparatus of FIG. 1in an activated configuration without the retention ring and a releasepaper backing, and with its microneedle assembly in a flush position, inaccordance with the first embodiment.

FIG. 3 is like FIG. 2, except for being a top plan view.

FIG. 4 is a partially exploded pictorial view of the drug deliveryapparatus of FIG. 1 without the retention ring.

FIG. 5 is an isolated, side cross-sectional view of a receptaclesubassembly of the drug delivery apparatus of FIG. 1.

FIG. 6 is a schematic pictorial, cross-sectional view of a portion of asupport structure and microneedle assembly of the receptacle subassemblyof FIG. 5.

FIG. 7 is an isolated, schematic, bottom pictorial view of a frame orbezel of the support structure of FIG. 6.

FIG. 8 is an isolated, top pictorial view of a cartridge subassembly ofthe drug delivery apparatus of FIG. 1.

FIG. 9 is a bottom pictorial view of the cartridge subassembly of FIG.8.

FIG. 10 is a schematic, side cross-sectional view of the cartridgesubassembly of FIG. 8.

FIG. 11 is an isolated, top pictorial view of a controller subassemblyof the drug delivery apparatus of FIG. 1, wherein the controllersubassembly is in its unactuated state.

FIG. 12 is a bottom pictorial view of the controller subassembly of FIG.11.

FIG. 13 is a side cross-sectional view of the controller subassembly ofFIG. 11.

FIG. 14 is an exploded pictorial view of the controller subassembly ofFIG. 11.

FIG. 15 is a pictorial, side cross-sectional view of the drug deliveryapparatus of FIG. 1 in the preactivated configuration without theretention ring.

FIG. 16 is a schematic view like FIG. 15, except that the drug deliveryapparatus is in an intermediate configuration between the preactivatedand activated configurations.

FIG. 17 is a schematic view like FIG. 15, except that the drug deliveryapparatus is shown in the activated configuration.

FIGS. 18 and 19 schematically illustrate a latching mechanism of thecontroller subassembly being opened in response to the drug deliveryapparatus being in the activated configuration.

FIG. 20 is a schematic view like FIG. 15, except that the drug deliveryapparatus is shown in its fully-activated or post-activatedconfiguration.

FIGS. 21 and 22 are isolated pictorial views of opposite sides of alower support structure of the drug delivery apparatus, in accordancewith a second embodiment, or the like.

FIG. 23 is a pictorial, side cross-sectional view of the drug deliveryapparatus in the preactivated configuration without the retention ring,in accordance with the second embodiment, or the like.

FIG. 24 is an enlarged view of a portion of FIG. 23.

DETAILED DESCRIPTION

Exemplary embodiments are described below and illustrated in theaccompanying drawings, in which like numerals refer to like partsthroughout the several views. The embodiments described provide examplesand should not be interpreted as limiting the scope of the inventions.Other embodiments, and modifications and improvements of the describedembodiments, will occur to those skilled in the art, and all such otherembodiments, modifications, and improvements are within the scope of thepresent invention.

In the following, a very brief and general initial discussion of a drugdelivery apparatus 10 of a first embodiment is followed by more detaileddiscussions, such as more detailed discussions of the separatesubassemblies of the apparatus 10. Referring to FIG. 1, the apparatus 10is shown in its preactivated configuration, and a retention device,which is shown for example as being in the form of a retention ring 12,is mounted to the apparatus. The retention ring 12 is for restrictingthe apparatus 10 from being transitioned from the preactivatedconfiguration shown, for example, in FIG. 1, to an activatedconfiguration shown, for example, in FIGS. 2 and 3.

Referring to the partially exploded view of FIG. 4, the apparatus 10 maybe characterized as including multiple main subassemblies that each maybe self-contained. The main subassemblies may include a receptacle 14, acartridge 16 or other suitable container or reservoir for being movablymounted in the receptacle, and a mechanical controller 18 mounted to thecartridge. Optionally, the cartridge 16 and controller 18 may becharacterized as together forming one of the main subassemblies.

A protective release paper backing 20 may cover an adhesive backing ofat least one deformable membrane 22 (FIGS. 2 and 15-17) that is mountedto respective surfaces of the receptacle 14. After removing anyprotective backing 20, or the like, and preferably (e.g., optionally)while the apparatus 10 is in its fully assembled configuration shown inFIG. 1, the receptacle 14 may be attached to a user's (e.g., patient's)skin by way of the adhesive-backed deformable membrane 22. Thedeformable component or membrane 22 may be referred to as an adhesivefastener, or more generally a fastener, for fastening at least a frameor housing of the receptacle 14 to the skin of a user, as will bediscussed in greater detail below.

The receptacle 14 of the first embodiment includes a microneedleassembly or array 24 (FIGS. 5, 6 and 15-17) having microneedles forpenetrating the user's skin, such as for providing a fluid that may bein the form of a liquid drug formulation into the user's skin. Themicroneedle assembly 24 may be more generally referred to as a devicefor engaging the skin of a patient or other user, and dispensing thedrug formulation to the user's skin, such as by dispensing the drugformulation into the epidermis portion of the user's skin. In contrastto how the apparatus 10 is shown in FIG. 2, it is typical for at leastthe tips of the microneedles of the microneedle assembly 24 to beprotruding outwardly through a lower opening of the receptacle 14. As amore specific example, while the apparatus 10 is in its activatedconfiguration and the microneedle array 24 is penetrating the user'sskin, at least the tips of, or the entire lengths of, the microneedlesare typically protruding outwardly through a lower opening of thereceptacle 14.

Very generally described, the cartridge 16 is in the form of orcomprises at least one storage container or reservoir that typicallyfully contains the liquid drug formulation in a hermetically sealedstate during at least the preactivated configuration of the apparatus10. In the preactivated configuration, the interior of thecartridge-like storage container 16 (e.g., reservoir) is out of fluidcommunication with the microneedle assembly 24. In contrast, while theapparatus 10 is in the activated configuration, the interior of thestorage container 16 is in fluid communication with the microneedleassembly 24, as will be discussed in greater detail below.

With the apparatus 10 oriented as shown in FIG. 1 and in thepreactivated configuration, an activation device or pushing mechanismthat may be in the form of a button-like outer end of a frame or housing26 of the controller 18 extends outwardly through an opening of thereceptacle 14. The apparatus 10 transitions from the preactivatedconfiguration to the activated configuration in response to thebutton-like end of the controller housing 26 being manually pushedinwardly relative to the receptacle 14. In the first embodiment, thetransition from the preactivated configuration to the activatedconfiguration includes relative movement between respectivesubassemblies of the apparatus 10. The button-like end of the controllerhousing 26 may be configured differently and/or replaced with any othersuitable component, such as a pushing mechanism, for triggering thetransition from the preactivated configuration to the activatedconfiguration. As will be discussed in greater detail below, thecontroller's housing 26 may be referred to as a pushing mechanism, ormore specifically a pushbutton, or the like, for actuating the apparatus10.

The receptacle 14, cartridge 16 and controller 18 may be originallyfabricated as components that are separate from one another, and then berespectively mounted to one another. For example, the controller 18 maybe conveniently mounted to the cartridge 16 by way of at least onemechanical connection and/or any other suitable fastening technique.Similarly, the cartridge 16 may be conveniently mounted to thereceptacle 14 by way of at least one mechanical connection and/or anyother suitable fastening technique. Each of, a majority of, or at leastsome of the mechanical connections may be at least partially defined byconnector parts for forming connections, and each or at least some ofthe connections may be snap-fit connections, wherein each snap-fitconnection may comprise a flexible, resilient latch. One or more of theconnections may be for releasably securing the apparatus 10 in thepreactivated configuration. Also, connector parts of the apparatus 10may be configured for arresting relative movement between features ofthe apparatus and securing the apparatus in the activated configuration,as will be discussed in greater detail below.

Referring primarily to FIG. 5, the receptacle 14 of the first embodimentincludes a compound frame or housing having an outer frame or body 30and an inner frame or body 32. The outer body 30 of the receptacle'shousing includes at least one sidewall 34 extending at least partiallyaround an interior space. In the first embodiment, the at least onesidewall 34 is in the form of a single sidewall 34 configured insubstantially frusto-conical shape, so that the interior space of theouter body 30 is substantially frusto-conical. An annular upper edge ofthe sidewall 34 extends around an upper opening 36 to the interior spaceof the outer body 30. The lower edge of the sidewall 34 terminates as anoutwardly extending annular attachment flange 38 and/or the attachmentflange 38 extends outwardly from an annular lower edge of the sidewall34. The attachment flange 38 extends around a lower opening to theinterior space of the outer body 30. The flange 38 may be referred to asan attachment flange because the adhesive membrane 22 is typicallyassociated with the attachment flange for attaching the apparatus 10 tothe skin of a user, as will be discussed in greater detail below.

For ease of understanding in this detailed description section of thisdisclosure, positional frames of reference, such as “upper” and “lower,”are used and can be understood with reference to the orientation of theapparatus 10 or features thereof in the drawings. However, the presentinvention is not limited to the positional frames of reference used inthis detailed description section of this disclosure because, forexample, the apparatus 10 of the first embodiment is configured so thatit may be used in both inverted and uninverted positions.

With continued reference to FIG. 5, the central axis of the outer body30, around which the frusto-conical sidewall 34 of the outer bodyextends, may serve as a frame of reference that may be used throughoutthis detailed description section of this disclosure for ease ofunderstanding, wherein an axial direction extends along (e.g., parallelto) the outer body's central axis, and radial directions extendoutwardly from (e.g., perpendicular to) the outer body's central axis.Further regarding the axial direction, inner and outer axial positionsor directions may be established relative to the center of a respectivefeature, such as relative to the position halfway between the upper andlower openings of the outer body 30. For example the button-like end ofthe controller housing 26 extends axially outwardly through the upperopening 36 of the housing of the receptacle 14. As another example, asubstantial portion of the outer body 30 is positioned radiallyoutwardly from the inner body 32. Whereas one or more frames ofreference are established for use in this detailed description sectionof this disclosure for ease of understanding, the present invention mayalso be described and understood with reference to other suitable framesof reference, such that the present invention is not limited to theframes of reference used in this detailed description section of thisdisclosure.

Further regarding the frusto-conical shape of the sidewall 34 of theouter body 30 and the central axis of the outer body, numerous of thefeatures of the apparatus 10 that are positioned in the interior spaceof the outer body may have a substantially annular shape and may besubstantially coaxially arranged with the outer body. Alternatively, theouter body 30 and the features of the apparatus 10 that are positionedin the interior space of the outer body may be shaped differently. Forexample, the at least one sidewall 34 of the outer body 30 may be in theform of multiple sidewalls that collectively extend around the interiorspace of the outer body, wherein the sidewalls may respectively meet atcorners, or the like. Accordingly, features of the apparatus 10 that arepositioned in the interior space of the outer body 30 may alternativelyhave configurations having corners that generally correspond to thecorners of the outer body. For example, for each sidewall of thesidewalls of this disclosure, the sidewall may be segmented so as to bein the form of multiple sidewalls that respectively meet a corner, orthe like. Similarly, other features of this disclosure may be segmentedor configured in any suitable manner.

As best understood with continued reference to FIG. 5, the inner body 32of the compound housing of the receptacle 14 is positioned in theinterior space defined by the compound housing's outer body 30. In thefirst embodiment, the outer body 30 is constructed of a material that ismore flexible (e.g., has a greater modulus of elasticity or a greaterbending modulus) than the material of the inner body 32, so that atleast a portion of the outer body may flex relative to the inner body.The inner body 32 is mounted to the interior of the outer body 30 by wayof one or more mechanical connections, adhesive material and/or anyother suitable fastening technique. Where practicable and in accordancewith one aspect of this disclosure, mechanical connections may be usedinstead of using adhesive materials.

The inner body 32 includes an annular seat flange 42 extending radiallyoutwardly from an axially extending cylindrical sidewall 44 of the innerbody. The outer body 30 includes a shoulder engaged in a crotch definedbetween the seat flange 42 and sidewall 44 of the inner body 32. Theupper end of the sidewall 44 is engaged in an interior annular recess inthe outer body 30, and the outer end of the seat flange 42 engagesagainst the inner surface of the sidewall 34 of the outer body.Alternatively, the outer and inner bodies 30, 32 of the frame or housingof the receptacle 14 may be constructed of the same type of material andthey may be integrally formed with one another. Notwithstanding, forease of understanding in this detailed description section of thisdisclosure, the housing of the receptacle 14 may be designated by thenumerals 30, 32. At least the receptacle's frame or housing 30, 32 isfor being fastened to a user of the apparatus 10, as will be discussedin greater detail below.

The receptacle 14 of the first embodiment further includes a support orsupport assembly, and one or more flexible or deformable components. Thedeformable components may include the deformable membrane 22 and a forceprovider that may be in the form of or comprise at least one metal, coilcompression spring 46. In the first embodiment, the support assembly ofthe receptacle 14 includes a first, radially outer support structure 50that is movably mounted in the housing 30, 32, and the support assemblyfurther includes a second, radially inner support structure 52 that isfixedly mounted to the outer support structure 50. As an example, thesupport structures 50, 52 may be connected to one another by one or moresnap-fit connections, wherein each snap-fit connection may comprise aflexible, resilient latch, as will be discussed in greater detail below.

The microneedle assembly 24 may be fixedly mounted to the inner supportstructure 52. For ease of understanding in this detailed descriptionsection of this disclosure, the support assembly of the receptacle 14may be designated by the numerals 50, 52. In the first embodiment, themicroneedle assembly 24 is movably mounted to the housing 30, 32 by wayof the support assembly 50, 52, deformable membrane 22 and spring 46.The deformable membrane 22 and spring 46 may optionally be referred toas being parts of the support assembly 50, 52.

The outer support structure 50 may include or be in the form of a sleeve50 configured for reciprocative sliding within the housing 30, 32. Thesleeve 50 includes an annular seat flange 54 extending radiallyoutwardly from the lower end of the main sidewall of the sleeve. At theupper end of the sleeve 50, the annular inner corner may be rounded, sothat it comprises an annular beveled surface 58, or the like.

The sleeve 50 further includes a series of spaced apart, flexible tabsor latches 56 that extend radially inwardly from the main sidewall ofthe sleeve, wherein considered collectively this series extendsannularly. A majority of, at least some of, or each of the tabs orlatches 56 may include a protrusion at its free end, wherein theprotrusion extends radially inwardly from the free end of the tab orlatch. The tabs or latches 56 may be connector parts, or morespecifically latch-like snap-fit connector parts, as will be discussedin greater detail below. Whereas the connector latches 56 of the sleeve50 of the first embodiment may be integrally formed with the sleeve,these connector parts may alternatively be originally formed separatelyfrom the sleeve and they may be mounted to, or otherwise associatedwith, the receptacle 14 in any suitable manner. The latches 56 may beproximate a first end of the support structure or sleeve 50, whereas themicroneedle assembly 24 may be proximate a second end of the sleeve, aswill be discussed in greater detail below

The spring 46 is typically a coil spring that extends around both thesidewall of the sleeve 50 and the sidewall of the inner body 32 of thecompound housing 30, 32. The opposite ends of the spring 46 arerespectively engaged against surfaces of the seat flanges 42, 54, sothat the seat flanges 42, 54 serve as seats for the spring. The innerbody 32 of the compound housing 30, 32 may be referred to as a support,seat and/or guide since, for example, the seat flange 42 of the innerbody 32 may serve as a seat for the spring 46. As another example, theradially outer surface of the lower portion of the sidewall of the innerbody 32 may serve as a guide for guiding axial compression and expansionof the spring 46. In addition, the radially inner surface of the innerbody 32 may serve as a guide for guiding axial, sliding relativemovement between the inner body and the sleeve 50.

As will be discussed in greater detail below, the spring 46 may bereferred to as a force provider for indirectly forcing the microneedleassembly 24 outwardly relative to the housing 30, 32 of the receptacle14. More generally, the receptacle 14 includes a force provider forforcing the microneedle assembly 24 outwardly relative to the housing30, 32. The force provider may include at least the spring 46, one ormore of the springs 46, and/or one or more other suitable forceproviding features that may be in the form of elastic objects, as willbe discussed in greater detail below.

The deformable membrane 22 may be referred to as an arresting device orretainer that is for restricting the spring 46 or any other suitableforce provider from separating the receptacle's support assembly 50, 52(and thus the microneedle assembly 24) from the receptacle's housing 30,32. In one embodiment, the spring 46 or other suitable force providermay be able to push the receptacle's support assembly 50, 52 (and thusthe microneedle assembly 24) out of the receptacle's housing 30, 32 werein not for the arresting or retaining functions provided by thedeformable membrane 22. Alternatively or in addition, these arresting orretaining functions may be provided by one or more other features of theapparatus 10.

As shown in FIG. 5, an annular channel member 60 is fixedly mounted tothe lower end of the sleeve 50 for traveling with the sleeve. Thechannel member 60 includes a centrally open, annular attachment plate 62and axially extending annular mounting and arresting flanges 64, 66. Theflanges 64, 66 extend inwardly respectively from the inner and outerperipheral edges of the attachment plate 62. The upper edge of themounting flange 64 may be fixedly mounted to the lower end of the sleeve50 so that the mounting flange may function as a spacer, standoff, orthe like, so that a gap is defined between the attachment plate 62 andthe seat flange 54 of the sleeve 50. Alternatively, the gap may beomitted or provided in any other suitable manner.

The flange 66 may be referred to as arresting flange(s), arrestinglobe(s), or the like, because an annular, beveled upper surface of theat least one arresting flange 66, or the like, may engage the innersurface of the sidewall 34 of the outer body 30 for restricting relativemovement between the compound housing 30, 32 and the sleeve 50 in afirst direction in response to predetermined compression of the outerspring 46. More specifically, the arresting lobe(s), arresting flange66, or the like, and the sidewall 34 of the outer body 30 may becooperatively configured for restricting the microneedle assembly 24from being pushed too far into the interior of the receptaclesubassembly 14 during use of the apparatus 10, as will be discussed ingreater detail below.

The plate 62 may be referred to as an attachment plate because theadhesive membrane 22 is typically attached to the attachment plate forat least partially attaching the apparatus 10 to the skin of a user, aswill be discussed in greater detail below. The channel member 60 may beconstructed of a material that is more flexible than the material of thesleeve 50, as will be discussed in greater detail below. Alternatively,the sleeve 50 and channel member 60 may be constructed of the same typeof material and/or be engaged and connected to one another in any othersuitable manner, or they may be integrally formed with one another.Accordingly, the channel member 60 may be characterized as being part ofthe sleeve 50 and vice versa.

Referring also to FIG. 6, the inner support structure 52 includes aframe 70 and a backing structure 72. As at least alluded to above, thebacking structure 72 is typically fixedly connected to the sidewall ofthe sleeve 50 for traveling therewith, and the periphery of themicroneedle assembly 24 is fixedly mounted to the backing structure.More specifically, the periphery of the microneedle assembly 24 isfixedly mounted between the frame 70 and backing structure for movingtherewith. The microneedle assembly 24 may be mounted between the frame70 and backing structure 72 by way of one or more mechanical connectionssuch as an interference fit, adhesive material and/or any other suitablefastening technique, as will be discussed in greater detail below.

As examples, the microneedle assembly 24 may be configured as disclosedin one or more of WO 2012/020332 to Ross, WO 2011/070457 to Ross, WO2011/135532 to Ross, US 2011/0270221 to Ross, and US 2013/0165861 toRoss, wherein each of these documents is incorporated herein byreference in its entirety. Generally, the microneedle assembly 24 of theapparatus 10 may have any suitable configuration known in the art fordelivering a fluidic drug formulation into and/or through the user'sskin, such as by being configured to include one or more microneedles 74extending outwardly from a suitable substrate or support, wherein thissubstrate or support may be referred to as a support plate 76 in thisdetailed description section for ease of understanding and not for thepurpose of limiting the scope of this disclosure. As shown in FIG. 6,the support plate 76 has a top surface 78 (e.g., backside) and a bottomsurface 80, and multiple microneedles 74 extend outwardly from thebottom surface 80. The support plate 76 and microneedles 74 maygenerally be constructed from a rigid, semi-rigid or flexible sheet ofmaterial, such as a metal material, a ceramic material, a polymer (e.g.,plastic) material and/or any other suitable material. For example, thesupport plate 76 and microneedles 74 may be formed from silicon by wayof reactive-ion etching, or in any other suitable manner.

The support plate 76 typically defines one or more passageways, whichmay be referred to as apertures, extending between, and open at each of,the top and bottom surfaces 78, 80 for permitting the drug formulationto flow therebetween. For example, a single aperture may be defined inthe support plate 76 at the location of each microneedle 74 to permitthe drug formulation to be delivered from the top surface 78 to suchmicroneedle 74. However, in other embodiments, the support plate 76 maydefine any other suitable number of apertures positioned at and/orspaced apart from the location of each microneedle 74.

Each microneedle 74 of the microneedle assembly 24 may include a basethat extends downwardly from the bottom surface 80 and transitions to apiercing or needle-like shape (e.g., a conical or pyramidal shape or acylindrical shape transitioning to a conical or pyramidal shape) havinga tip that is distant from the bottom surface 80. The tip of eachmicroneedle 74 is disposed furthest away from the support plate 76 andmay define the smallest dimension (e.g., diameter or cross-sectionalwidth) of each microneedle 74. Additionally, each microneedle 74 maygenerally define any suitable length between its base and its tip thatis sufficient to allow the microneedles 74 to penetrate the stratumcorneum and pass into the epidermis of a user. It may be desirable tolimit the length of the microneedles 74 such that they do not penetratethrough the inner surface of the epidermis and into the dermis, whichmay advantageously help minimize pain for the patient receiving the drugformulation.

In one embodiment, each microneedle 74 may have a length of less thanabout 1000 micrometers (um), such as less than about 800 um, or lessthan about 750 um, or less than about 500 um (e.g., a length rangingfrom about 200 um to about 400 um), or any other subranges therebetween.In one specific example, the microneedles 74 may have a length of about290 um. The length of the microneedles 74 may vary depending on thelocation at which the apparatus 10 is being used on a user. For example,the length of the microneedles 74 for an apparatus to be used on auser's leg may differ substantially from the length of the microneedles74 for an apparatus to be used on a user's arm. Each microneedle 74 maygenerally define any suitable aspect ratio (i.e., the length over across-sectional width dimension of each microneedle 74). In certainembodiments, the aspect ratio may be greater than 2, such as greaterthan 3 or greater than 4. In instances in which the cross-sectionalwidth dimension (e.g., diameter) varies over the length of eachmicroneedle 74, the aspect ratio may be determined based on the averagecross-sectional width dimension.

Each microneedle 74 may define one or more channels in fluidcommunication with the apertures defined in the support plate 76. Ingeneral, the channels may be defined at any suitable location on and/orwithin each microneedle 74. For example, the channels may be definedalong an exterior surface of each microneedle 74. As a more specificexample, each channel may be an outwardly open flute defined by theexterior surface of, and extending along the length of, a microneedle74. Alternatively and/or in addition, the channels may be definedthrough the interior of the microneedles 74 such that each microneedle74 forms a hollow shaft. Regardless, the channels may generally beconfigured to form a pathway that enables the drug formulation to flowfrom the top surface 78 of the support plate 76, through the aperturesand into the channels, at which point the drug formulation may bedelivered into and/or through the user's skin. The channels may beconfigured to define any suitable cross-sectional shape. For example, inone embodiment, each channel may define a semi-circular or circularshape. In another embodiment, each channel may define a non-circularshape, such as a “v” shape or any other suitable cross-sectional shape.

The dimensions of the channels defined by the microneedles 74 may bespecifically selected to induce a capillary flow of the drugformulation. The capillary pressure within a channel is inverselyproportional to the cross-sectional dimension of the channel anddirectly proportional to the surface energy of the subject fluid,multiplied by the cosine of the contact angle of the fluid at theinterface defined between the fluid and the channel. Thus, to facilitatecapillary flow of the drug formulation through the microneedle assembly24, the cross-sectional width dimension of the channel(s) (e.g., thediameter of the channel) may be selectively controlled, with smallerdimensions generally resulting in higher capillary pressures. Forexample, in several embodiments, the cross-sectional width dimension ofthe channels may be selected so that, with regard to the width of eachchannel, the cross-sectional area of each channel ranges from about1,000 square microns (um²) to about 125,000 um², such as from about1,250 um² to about 60,000 um², or from about 6,000 um² to about 20,000um², or any other subranges therebetween.

The microneedle assembly 24 may generally include any suitable number ofmicroneedles 74 extending from its support plate 76. For example, in oneembodiment, the actual number of microneedles 74 included within themicroneedle assembly 24 may range from about 10 microneedles per squarecentimeter (cm²) to about 1,500 microneedles per cm², such as from about50 microneedles per cm² to about 1250 microneedles per cm², or fromabout 100 microneedles per cm² to about 500 microneedles per cm², or anyother subranges therebetween. The microneedles 74 may generally bearranged on the support plate 76 in a variety of different patterns, andsuch patterns may be designed for any particular use. For example, inone embodiment, the microneedles 74 may be spaced apart in a uniformmanner, such as in a rectangular or square grid or in concentriccircles. In such an embodiment, the spacing of the microneedles 74 maygenerally depend on numerous factors, including, but not limited to, thelength and width of the microneedles 74, as well as the amount and typeof drug formulation that is intended to be delivered through themicroneedles 74.

Each of the opposite sides of the microneedle assembly 24 may be coveredby (e.g., the microneedle assembly may include) one or more membranes(e.g., polymeric films). For example, the microneedles 74 may be coveredby one or more membranes that may optionally include nanotopography, asdisclosed by at least one of the documents previously incorporatedherein by reference. However, any embossing or nanotopography may beomitted. As another example, the top surface 78 of the support plate 76may be covered with one or more rate control membranes or other suitablemembrane(s). For example, a rate control membrane may be fabricated frompermeable, semi-permeable or microporous materials that are known in theart to control the rate of flow of drug formulations.

As best understood with reference to FIG. 6, at least a portion of themicroneedle assembly's support plate 76 may have a substantiallyrectangular periphery that is in the form of or includes a peripheralchannel 82 that (considering the support plate in isolation) isdownwardly open and may have an overall substantially rectangular shape,or any other suitable shape. Similarly, the backing structure 72 of thefirst embodiment may be tiered or step-shaped so as to include inner andouter channels 84, 86 that (considering the backing structure inisolation) are downwardly open and may have an overall rectangularshape, or any other suitable shape.

A substantially rectangular gasket 88 may be engaged in the innerchannel 84 and engaged securely against the margin of the rate controlmembrane and/or other suitable membrane that forms or is positioned atthe top surface 78 of the microneedle assembly 24. These secureengagements associated with the gasket 88 may result at least partiallyfrom the frame 70 being fixedly mounted to the backing structure. Morespecifically, the frame 70 may be fixedly mounted between the peripheralchannel 82 of the microneedle assembly 24 and the outer channel 86 ofthe backing structure 72. The frame 70 may be mounted between theperipheral and outer channels 82, 86 by way of one or more mechanicalconnections such as an interference fit, a mounting frame and/or anyother suitable fastening technique, as discussed in greater detailbelow. In the first embodiment, the microneedle assembly 24 issubstantially fixedly connected to backing structure 72 of the supportassembly of the receptacle 14 by way of the subject connections.

The frame 70 may be characterized as being a substantially rectangularbezel having substantially S-shaped cross-sections. The outer peripheraledge of the frame 70 may be mounted into the outer channel 86 by way of,for example, a press-fit, so that the outer peripheral edge of the frameis in compressing, opposing-face-to-face contact with a flange that ispart of or otherwise associated with (e.g., partially defines) the outerchannel, and the inner peripheral margin of the frame is in compressing,opposing-face-to-face contact with the bottom surface 80 of the supportplate 76. More specifically, the frame 70 engages against a surface ofthe peripheral channel 82 of the support plate.

Alternatively, the microneedle assembly 24 may be mounted to the backingstructure 72, sleeve 50 or housing 30, 32 in any suitable manner. Forexample, and as previously indicated, features of the apparatus 10 maybe configured differently than shown in the drawings. As a more specificexample, the frame 70, channels 82, 84, 86, gasket 88 and otherrectangular features may be in any other suitable shapes. As anotherexample, whereas the backing structure 72 is shown in the drawings asbeing a single, unitary part, it may be constructed of separate partsthat are connected to one another in any suitable manner. As anadditional example, the outer periphery of the frame 70 may be securedin the outer channel 86 through the use of one or more attachment ormounting features, as will be discussed in greater detail below.

In the embodiment shown in FIG. 6, a lower face 77 of the backingstructure 72, top surface 78 of the support plate 76, gasket 88 andinner channel 84 are cooperatively configured so that a peripherallyclosed gap 90 is defined between a portion of the radially inner surfaceof the gasket 88, a central portion of the lower face of the backingstructure 72, and the central portion of the rate control membraneand/or other suitable membrane that forms or is positioned at the topsurface 78 of the microneedle assembly 24. This peripherally closed gap90 may be referred to as a plenum chamber 90 that is preferablyhermetically sealed or closed, except for being open to the aperturesthat extend through the support plate 76 and a hole or supply passageway91 (FIGS. 5 and 24) extending through the backing structure 72.

Referring back to FIG. 5, the receptacle 14 further includes at leastone cannula 92 fixedly mounted to the backing structure 72 for movingtherewith. For example, a lower portion of the cannula 92 may be fixedlymounted in the supply passageway extending through the backing structure72 by way of one or more mechanical connections such as an interferencefit, adhesive material and/or any other suitable fastening technique.The lower open end of the cannula 92 is in fluid communication with theplenum chamber 90 (FIG. 6), and the upper open end of the cannula, whichis typically sharply pointed, extends axially upwardly from the backingstructure 72 for piercing a predetermined portion of the cartridge 16(FIGS. 4 and 8-10), as will be discussed in greater detail below. Thecannula 92 may extend through a sealing gasket 94 housed in a cavity ofthe backing structure 72 and/or sealing of the plenum chamber 90 may beprovided in any suitable manner.

With continued reference to FIG. 5, the deformable membrane 22 may be inthe form of a patch of double-sided pressure-sensitive adhesive tape,wherein the tape comprises a polymeric film with a relatively permanentadhesive material on one side and a relatively releasable adhesivematerial on the opposite side. The adhesively-coated, deformablemembrane patch 22 may be substantially in the shape of a disk with acentrally located round opening, wherein the microneedles 74 (FIG. 6)protrude outwardly through the central opening of the disk-shaped patch.The relatively permanent adhesive material is for permanently connectingthe radially inner marginal portion of the membrane patch 22 to theannular attachment plate 62, and the relatively permanent adhesivematerial is for permanently connecting the radially outer marginalportion of the membrane patch 22 to the annular attachment flange 38.Optionally, the channel member 60 may be omitted and the relativelypermanent adhesive material may connect the radially inner marginalportion of the membrane patch 22 to the seat flange 54 of the sleeve 50or to another suitable feature. Alternatively, the seat flange 54,annular channel member 60 and/or portions thereof may be part of theinner or lower support structure 52, as will be discussed in greaterdetail below.

The relatively releasable adhesive material is for releasably connectingthe membrane patch 22 to the user's skin for the purpose of fasteningthe apparatus 10 to the user. For example, the adhesives may be selectedfrom conventional adhesive materials, such as acrylic adhesivematerials. As a more specific example, the relatively releasableadhesive material may be a silicon adhesive material having at least tworelaxation modes, wherein the adhesive bond of the silicon adhesivematerial may be stronger in one mode than the other. For example, thesilicon adhesive may have a lower adhesive strength when the membranepatch 22 is slowly separated from the user's skin, as compared to whenthe membrane patch 22 is quickly separated from the user's skin. Thesilicone adhesive may be or may comprise a silicone gel. In this manner,the membrane patch 22 can be readily removed from the skin by the wearerafter use, while at the same time preventing the apparatus 10 from beinginadvertently or prematurely disengaged from the skin, for example, byaccidentally bumping or knocking the apparatus during use.

The protective backing 20 (FIG. 1), which may be present fortemporarily, removably covering the relatively releasable adhesivematerial of the membrane patch 22, may be in the shape of disk with acentrally located round opening, and an outwardly protruding pull tabmay protrude from the disk. The protective backing 20 may comprise aconventional paper-based material with a conventional release coatingthat is engaged against the relatively releasable adhesive material ofthe membrane patch 22, or the protective backing may be in any othersuitable configuration.

Referring to FIGS. 8-10, the receptacle or cartridge 16 (FIG. 2) mayinclude or be in the form of a storage container 16 for receiving andcontaining the drug formulation associated with the apparatus 10. Thecartridge-like storage container 16 of the first embodiment includes atleast one body 96 defining relatively wide and relatively narrowcavities 98, 100 (FIG. 10) that are open to one another, such as by wayof a passageway defined in the body 96 and extending between and open toeach of the wide and narrow cavities. In the first embodiment, thepassageway defined in the body 96 is contiguous with both of thecavities 98, 100.

As best understood with reference to FIG. 10, the wide cavity 98 issubstantially concave or substantially bowl shaped, such that at leastone surface of the body 96 that defines the wide cavity is concave innumerous cross-sections. That is, the wide cavity 98 may be at leastpartially defined by a substantially concave wall of the body 96, andthe substantially concave wall may more specifically be a substantiallybowl-shaped wall.

As also best understood with reference to FIG. 10, the narrow cavity 100includes a cylindrical section that tapers to a frustoconical section.As shown in FIG. 10, one end of the passageway connecting the cavities98, 100 is open at the highest point of the tip of narrow cavity 100,and the opposite end of the passageway connecting the cavities 98, 100is open at the lowest point of the substantially bowl-shaped wide cavity98. That is, the respective end of the subject passageway may be openproximate, or more specifically at, the central portion of thesubstantially concave wall that at least partially defines the widecavity 98. Even more specifically, the respective end of the subjectpassageway may be open proximate, or more specifically at, the centralportion of the substantially bowl-shaped wall that at least partiallydefines the wide cavity 98. The cavities 98, 100 and associatedpassageway may be configured differently than discussed above.Nonetheless, for ease of understanding in this detailed descriptionsection of this disclosure, relative terms such as “narrow” and “wide”are used for identification purposes, even though the present inventionis not limited so such terms or relative sizes.

The body 96 defines opposite outer openings that are respectivelypositioned at opposite ends of the body. These openings are open to andcontiguous with the cavities 98, 100, respectively. The outer opening tothe wide cavity 98 is closed by a relatively wide closure 102, and theouter opening to the narrow cavity 100 is closed by a relatively narrowclosure 104. The wide and narrow closures 102, 104 are respectivelymounted proximate, or more specifically mounted to, the opposite ends ofthe body 96.

The narrow closure 104 includes a cap 106, or the like, securing aself-sealing member over the outer opening to the narrow cavity 100. Theself-sealing member may be a disk-shaped self-sealing septum 108 or anyother suitable self-sealing member. The cap 106 secures the self-sealingseptum 108 over the outer opening to the narrow cavity 100, so that theself-sealing septum is in compressed, opposing-face-to-face contact withan end of a flange of the body 96 that defines the outer opening to thenarrow cavity. In this configuration, the septum 108 at least partiallycloses, or more specifically completely closes, the outer opening to thenarrow cavity 100.

The cap 106 may generally include a disk 110, or the like, with acentrally located opening for providing access to the self-sealingseptum 108. The cap 106 may further include an annular flange 112extending axially from a peripheral edge of the disk 110. The cap 106may be mounted at least by the flange 112 of the cap 106 being engagedto and mounted to a corresponding flange of the body 96 by way of one ormore mechanical connections such as an interference fit, adhesivematerial, a weld joint (e.g., spin welding, ultrasonic welding, laserwelding or heat staking) and/or any other suitable fastening technique.The flange 112 may be described as being a cylindrical flange or acylinder 112, and the disk 110 may be referred to as an annular flangeextending inwardly from an end edge of the cylinder 112.

The wide closure 102 includes a cap 114, or the like, securing a movablemember over the outer opening to the wide cavity 98. The movable memberover the outer opening to the wide cavity 98 may be a disk-shapeddeformable membrane 116. The cap 114 may secure the disk-shaped memberor deformable membrane 116 over the outer opening to the wide cavity 98so that the deformable membrane 116 is in compressed,opposing-face-to-face contact with an end face of the body 96 thatdefines the outer opening to the wide cavity. In this configuration, themembrane 116 at least partially closes, or more specifically completelycloses, the outer opening to the wide cavity 98.

Generally described, the cap 114 may include a disk 118, and inner andouter annular flanges 120, 122 extending axially in opposite directionsfrom the disk. The disk 118 has a centrally located opening forproviding access to the deformable membrane 116. Referring to FIG. 10,the cap 114 may be mounted at least by the outer flange 122 of the cap114 being engaged to and mounted to a corresponding flange 124 of thebody 96, such as by way of an annular flange 126 extending radiallyinwardly from an end of the outer flange 122 and engaging against an endedge of the flange 124 of the body. The inner and outer flanges 120, 122may be described as being integrally formed coaxial inner and outercylinders 120, 122, wherein an annular shoulder 128 of the cap 114 maybe defined at the transition between the inner and outer cylinders 120,122 and/or flanges 120, 122. Alternatively or additionally, the outerflange 122 of the cap 114 may be mounted to the flange 124 of the body96, by way of one or more mechanical connections such as an interferencefit, adhesive material, a weld joint (e.g., spin welding, ultrasonicwelding, laser welding or heat staking) and/or any other suitablefastening technique.

Referring initially to FIG. 8, the cap 114 or portions thereof may bereferred to as structure for supporting and/or defining connector partsfor at least partially forming mechanical connections that may bereleasable. For example, some of the connector parts of the cap 114 maybe in the form of a series of spaced apart, flange-like, arcuateprotruding connector parts 130 extending radially outwardly from theinner cylinder or flange 120. As another example, other of the connectorparts of the cap 114 may be in the form of outwardly oriented or open,upper and lower annular groove connector parts 132, 134 that are definedby the outer cylinder or flange 122 and spaced apart from one anotheralong the length of the cap 114. Whereas the connector parts 130, 132,134 of the cap 114 of the first embodiment may be integrally formed withthe cap 114, these connector parts may alternatively be originallyformed separately from the cap 114 and they may be mounted to, orotherwise associated with, the cartridge 16 in any suitable manner. Moregenerally, the connector parts 130, 132, 134 extend outwardly from thebody 96 of the receptacle or cartridge 16, and the connector parts 130,132, 134 may be connected to or otherwise associated with the body 96 inany suitable manner.

Referring to FIGS. 11-14, and initially primarily to FIG. 14, thecontroller 18 includes the controller housing 26; an activation deviceor pushing mechanism that may be in the form of a plunger 140, or thelike; at least one force provider that may be in the form of or compriseat least one metal, coil compression spring 142 positioned between thecontroller housing and the plunger for moving the plunger relative tothe controller housing; and a latching mechanism 144 for selectivelyrestricting and allowing relative movement between the housing and theplunger. The controller 18 may also include a guide member or disk 146and elastic ring 148.

As will be discussed in greater detail below, the spring 142 may bereferred to as a force provider for forcing the plunger 140 outwardlyrelative to the controller housing 26. More generally, the controller 18includes a force provider for forcing the plunger 140 outwardly relativeto the controller housing 26, wherein the force provider may comprisethe spring 142, one or more of the springs 142, and/or one or more othersuitable force providing features that may be in the form of elasticobjects, as will be discussed in greater detail below. In theillustrated embodiment, the first force provider or spring 46 (FIG. 5)is larger than, and may be stronger than, the second force provider orspring 142, as will be discussed in greater detail below.

The controller housing 26 includes at least one wall, or morespecifically a pair of spaced apart arcuate walls 150 extending axiallyfrom a terminal portion that may be in the form of a plate or disk 152.The terminal portion or disk 152 may be generally or at least somewhatdome-shaped and may serve as a pushbutton or portion of a pushbutton forbeing manually pressed, as will be discussed in greater detail below.Similarly, the controller housing 26 as a whole, or portions thereof,may be referred to as a pushbutton, as will be discussed in greaterdetail below. Although the controller housing 26 and/or features thereofmay be configured differently, for ease of understanding and not forpurposes of narrowing the scope of the present invention, the controllerhousing 26 may be referred to as a button 26, and the disk 152 may bereferred to as a button plate or button disk 152 in this detaileddescription section of this disclosure. The arcuate walls 150 extendalong, but are spaced apart inwardly from, the periphery of the buttondisk 152, so that an annular shoulder 154 of the button disk extendsradially outwardly from the arcuate walls 150. A groove in the arcuatewalls 150 defines arcuate shoulders 156 (FIG. 12).

The arcuate walls 150 may each be referred to as a structure forsupporting and/or defining connector parts for at least partiallyforming mechanical connections. For example, the connector parts of thearcuate walls 150 may be in the form of a series of spaced apart,flange-like, arcuate protruding connector parts 158 (FIG. 12) extendingradially inwardly from the arcuate walls 150. Whereas the connectorparts 158 of the controller housing 26 may be integrally formed with thecontroller housing 26, these connector parts may alternatively beoriginally formed separately from the controller housing and they may bemounted to, or otherwise associated with, the controller 18 in anysuitable manner.

The controller housing 26 includes a central protrusion, guide orguidepost 160 (FIGS. 13 and 14) extending coaxially from the inner sideof the button disk 152 for extending into, and guiding, the coil spring142 and the plunger 140. The plunger 140 includes a cylindrical shaft162 (FIG. 14) coaxially extending from a domed head 164. Outwardly open,upper and lower recesses that may be in the form of annular grooves 166,168 (FIG. 13) are defined in the plunger's shaft 162. The at least onewall 150 of the controller housing 26 extends at least partially aroundshaft 162, which extends at least partially around the spring 142, whichextends at least partially around the guide or guidepost 160.

Referring to FIGS. 12 and 14, the latching mechanism 144 has oppositeends that extend at least partially into, or more specifically at leastpartially through, the holes, slots or gaps between the arcuate walls150. Each end of the latch 144 includes an axially protruding, arcuateskirt portion 172, and a radially outwardly protruding actuator oractuation tab having an arcuate beveled surface 170. For each of theopposite ends of the latch 144, the beveled actuating surface 170 andthe skirt portion 172 each extend substantially all the way between theadjacent ends of the arcuate walls 150, so that the ends of the latchobstruct, or more specifically substantially close, the holes, gaps orslots between adjacent ends of the arcuate walls 150.

Referring to FIGS. 14, 18 and 19, the latch 144 further includes a pairof locking members, locking bars, or locking arms 174 that extendbetween the opposite ends of the latch. While the plunger 140 is in itsretracted position, its shaft 162 extends through a space definedbetween middle portions of the locking arms 174, and the middle portionsof the locking arms extend into the upper groove 166 in the shaft 162while the latch is in its locking or unactuated state. In this state,the locking arms 174 one or more shoulders of the shaft 162, whereinthese shoulders that at least partially define the upper annular groove166. Pairs of guide members or guide arms 176 may extend arcuately fromproximate the opposite ends of the latch for respectively engaging theinterior surfaces of the arcuate walls 150. Whereas the latch 144 hasbeen described as having features in pairs, the latch may be configureddifferently, such as by omitting one of each pair, or the like.

Referring to FIG. 13, the inner periphery of the guide disk 146 may beretained in the upper groove 168 in the shaft 162 of the plunger 140.The elastic ring 148 may be positioned between, and in opposingface-to-face contact with each of, the guide disk 146 and the guide arms176 of the latch 144. The elastic ring 148 may engage the inner faces ofthe skirt portions 172 for helping to maintain the latch 144 in itsunactuated state and/or the latch 144 may be made out of a elasticmaterial that biases the latch toward its unactuated state.

The at least one arcuate wall 150 of the pushbutton or controllerhousing 26 extends at least partially around an interior space. At leasta portion of each of the plunger 140, spring 142, latch 144, guide disk146, elastic ring 148, guidepost 160 and/or shaft 162 may be positionedin the interior space that the at least one arcuate wall 150 extendsaround. Substantially the entirety of each of the plunger 140, spring142, latch 144, guide disk 146, elastic ring 148, guidepost 160 and/orshaft 162 may be positioned in the interior space that the at least onearcuate wall 150 extends around. Other configurations of the controller18 are also within the scope of this disclosure.

Whereas examples of some methods that may be associated with theapparatus 10 have been discussed above, others are discussed in thefollowing, in accordance with the first embodiment. For example andreferring back to FIG. 5, the microneedle assembly 24 may besubstantially fixedly mounted to the support assembly 50, 52, in themanner discussed above, either before or after the receptacle's supportassembly 50, 52 is movably mounted to the receptacle's housing 30, 32.The support assembly 50, 52 is movably mounted to the receptacle'shousing 30, 32 so that the support assembly 50, 52, and thus themicroneedle assembly 24 carried by the support assembly 50, 52, may bemoved inwardly and outwardly relative to the housing 30, 32.

With continued reference to FIG. 5, the support structure or supportassembly 50, 52 may be movably mounted to the housing 30, 32 bycompressing the respective force provider, which may comprise the spring47, between the support assembly 50, 52 and the housing 30, 32, and thenby connecting at least one deformable component, such as the deformablemembrane 22, between the support assembly 50, 52 and the housing 30, 32.The deformable membrane 22 is for simultaneously restricting expansionof the spring 47 and allowing relative movement between the supportassembly 50, 52 and the housing 30, 32. For example, the at least thedeformable membrane 22 may keep the support assembly 50, 52 and thespring 47 from falling away from, or more specifically out of, thehousing 30, 32. In this regard and reiterating from above, thedeformable membrane 22 may be referred to as an arresting device orretainer that is for restricting the spring 46 or any other suitableforce provider from separating the receptacle's support assembly 50, 52(and thus the microneedle assembly 24) from the receptacle's housing 30,32.

Further regarding the mounting of the support structure or assembly 50,52 to the housing 30, 32, manual compressing of the spring 47 may becomprised of causing a first relative movement between the supportassembly 50, 52 and the housing 30, 32. After the deformable membrane 22is installed, the support assembly 50, 52 and/or the housing 30, 32 maybe manually released, so that the spring 47 causes a second relativemovement between the support assembly 50, 52 and the housing 30, 32. Thesecond relative movement may be partially restricted by the deformablemembrane 22 and/or any other suitable features.

Generally described, the controller 18 may be assembled by substantiallycoaxially arranging its features as shown in FIG. 14, and thenrespectively bringing the features into contact with one another asshown in FIG. 13. More specifically, the subject force provider, whichmay comprise the spring 142, may be compressed between the pushbutton orcontroller housing 26 and the pushing mechanism or plunger 140. Thiscompressing may be achieved through relative movement between thecontroller housing 26 and plunger 140. As part of this or other relativemovement, the shaft 162 of the plunger 140 may be moved into and througha hole in the latching mechanism 144. The subject hole in the latchingmechanism 144 may be defined between the locking members or arms 174.The shaft 162 may pass into the hole in the latching mechanism 144 byway of the shaft pushing the locking arms 174 apart and enlarging thehole, wherein the locking arms may elastically move into the groove 166in the shaft 162 to arrest the subject relative movement and hold theplunger 140 in its retracted position. In this regard, the locking arms174 more specifically engage against at least one shoulder of the shaft162 for holding the plunger 140 in its retracted position, wherein thesubject shoulder of the shaft partially defines the groove 166. However,the subject shoulder(s) may be configured differently.

As best understood with reference to FIG. 19, the cartridge 16 andcontroller 18 being connected to one another and/or other features, suchas the guide disk 146 and support ring 148, are cooperative forrestricting axial movement of the latching mechanism 144. The cartridge16 and controller 18 may be connected to one another as shown in FIG. 2by causing relative axial movement between the cartridge and controllerso that the protruding connector parts 130 (FIG. 8) of the cartridgepass through the spaces defined between the protruding connector parts158 (FIG. 12) of the controller, and vise versa. The relative axialmovement may continue until the free edge of the inner flange 120 (FIGS.8 and 10) of the cartridge 16 and the guide disk 146 (FIGS. 12-14) ofthe controller 18 engage against one another, and the shoulder 128(FIGS. 8 and 10) of the cap 114 and the lower edges of the arcuate walls150 (FIGS. 11-13) of the controller housing 26 engage against oneanother. Then, through relative rotation between the cartridge 16 andcontroller 18, the protruding connector parts 130, 158 respectivelyengage behind one another, so that the cartridge and controller aremounted to one another by way of the protruding connector parts 130,158. Additionally or alternatively, the cartridge 16 and controller 18may be mounted to one another by way of any other suitable mechanicalconnections and/or any other suitable fastening techniques. For example,the connector parts 130, 158 may be supplemented with or replaced by oneor more weld joints that may be formed, for example, by spin welding,ultrasonic welding, laser welding, heat staking and/or any othersuitable technique. As another example, the cartridge 16 and controller18 may be connected to one another by one or more snap-fit connections,wherein each snap-fit connection may comprise a flexible, resilientlatch, as will be discussed in greater detail below.

As best understood with reference to FIG. 10, preparing the apparatus 10for use may include charging the reservoir or cartridge 16 with a drugformulation. The drug formulation may be injected through theself-sealing septum 108 into the narrow cavity 100, so that the drugformulation also flows into the wide cavity 98 by way of the passagewaybetween the narrow and wide cavities. For example, the drug formulationmay be injected through the self-sealing septum 108 using conventionalcharging devices that are conventionally used to fill conventional vialswith caps equipped with self-sealing septums. A charging device mayinclude coaxial needles for extending through the self-sealing septum108, wherein one of the needles draws a partial vacuum in the cavities98, 100 and the other needle injects the drug formulation. The drugformulation may substantially fill the interior of the cartridge 16 sothat any air may be substantially eliminated from the interior of thecartridge.

The cartridge 16 may be charged with a drug formulation either before orafter the cartridge 16 and controller 18 are mounted to one another.Irrespective, the cartridge 16 will typically be charged with a drugformulation under septic conditions. In one example, the interior volumeof the reservoir or cartridge 16 may be up to about 500 μL, and themicroneedle assembly 24 may be about 12.5 mm by about 12.5 mm. Inanother example, the interior volume of the reservoir or cartridge 16may be up to about 2 mL, and the microneedle assembly 24 may be about 25mm by about 25 mm. Other volumes and sizes are within the scope of thisdisclosure. For example, the volume the interior of the reservoir orcartridge 16 may be in a range of about 100 μL to about 2 mL or more.Those of ordinary skill in the art will understand how to makeappropriate use of cleanrooms and sterilization in association with theapparatus 10.

As best understood with reference to FIG. 4, the assembled togethercartridge 16 and controller 18 may optionally be encircled by theretention ring 12 (FIG. 12) and then be mounted into the receptacle 14by introducing the lower end of the cartridge 16 into the upper opening36 of the receptacle 14. As may be understood with reference to FIGS. 4,5, 8 and 15, there may be relative sliding between the protruding tipsof the latch connector parts 56 (FIGS. 4 and 5) and the outer housing orflange 122 (FIGS. 8-10) of the cartridge 16. The subject relativesliding may be in response to relative movement between the receptacle14 and the cartridge 16 while the cartridge is at least partiallypositioned in the interior space surrounded by the sleeve 50 (FIGS. 4and 5), and this relative movement may be caused by manually pushingdown on the button disk 152. The cartridge 16 and controller 18 may havebeen previously mounted to one another as discussed above, so they movewith one another in response to the button disk 152 being pushed.

The apparatus 10 is shown in its preactivated configuration in FIGS. 1and 15, although the retention ring 12 is omitted from FIG. 15. When thecartridge 16 and the controller 18 are being initially installed in thereceptacle 14, the relative movement between the receptacle 14 andcartridge 16 may be automatically arrested when the preactivatedconfiguration is reached. The relative movement between the receptacle14 and cartridge 16 may be arrested in response to engagement of atleast one obstruction for releasably securing the drug deliveryapparatus in the preactivated configuration. The obstruction maycomprise at least one releasable mechanical connection and/or at leastone retention device. For example, the retention ring 12 (FIG. 1) or anyother suitable retention device may engage between the shoulder 154(FIGS. 12 and 13) of the button disk 152 and the upper edge of thesleeve 50 (FIGS. 4 and 5) to arrest the relative movement when theapparatus 10 reaches the preactivated configuration.

In accordance with the first embodiment, the apparatus 10 is configuredso that at substantially the same time that the retention ring 12, orthe like, engages between the shoulder 154 of the button disk 152 andthe upper edge of the sleeve 50 to arrest the relative movement betweenthe receptacle 14 and cartridge 16 when the apparatus reaches thepreactivated configuration, the protruding tips of the latch connectorparts 56 (FIGS. 5 and 15) reach the lower groove connector part 134(FIGS. 8-10). When the protruding tips of the latch connector parts 56reach the lower groove connector part 134, the radially inwardly biasednature of the latch connector parts 56 may cause the protrusionsproximate the tips of the latch connector parts 56 to protrude into thelower groove connector part 134, to engage at least one edge or shoulderof the cartridge 16 that at least partially defines or is proximate thelower groove connector part 134, to form mechanical connections thatarrest the relative movement when the apparatus 10 reaches thepreactivated configuration. In the first embodiment, these mechanicalconnections are releasable snap-fit connections (e.g., the latchconnector parts 56 may be referred to as flexible, resilient latches),although they may comprise other suitable connections. The mechanicalconnectors defined by the latch and lower groove connector parts 56, 134may be referred to as at least one detent or at least one lowermechanical connector 56, 134. Optionally, at least one of the retentionring 12 or the lower mechanical connector 56, 134 may be omitted.

In the first embodiment, at least the lower mechanical connector 56, 134is a releasable connector that may be transitioned from a connectingstate to an unconnecting state in response to predetermined relativemovement between the receptacle 14 and the cartridge 16. For example,such predetermined relative movement between the receptacle 14 and thecartridge 16 may be caused by a force being used in an effort to causerelative movement between the receptacle and cartridge exceeding apredetermined amount. Accordingly, if the retention ring 12 is omittedfrom the apparatus 10 or removed from the apparatus and it is desirablefor the apparatus to be retained in the preactivated configuration, amethod may include any force seeking to cause the relative movementbetween the receptacle 14 and the cartridge 16 not exceeding apredetermined amount that would be sufficient for causing the lowermechanical connector 56, 134 to become disconnected.

With the apparatus 10 in its preactivated configuration shown FIG. 1,the protective backing 20 may be removed and the adhesive membrane 22may be engaged against a user's (e.g., patient's) skin to fasten theapparatus to the user's skin. The engagement will typically befacilitated through relative movement between the apparatus 10 and user.As the apparatus 10 is moved toward the user's skin, the microneedles ofthe microneedle assembly 24 may be the first features of the apparatus10 to touch the user's skin since the microneedle assembly 24 is biasedoutwardly from the receptacle 14 due to the action of the force providerthat may comprise the spring 46. That is, the microneedle assembly 24may engage the user's skin before the apparatus 10 is fastened to theuser. In the first embodiment, when the apparatus 10 is initiallyengaged against the user's skin, the microneedle assembly 24 is engagedagainst the user's skin, and the engaging of the microneedle assemblyagainst the user's skin causes or comprises compressing of the spring46.

The outwardly oriented, relatively releasable adhesive material of theadhesive membrane 22 fastens at least the receptacle's housing 30, 32 tothe user, such that the adhesive membrane 22 may be referred to as afastener. Alternatively, the fastening may be supplemented with, orreplaced by, any other suitable fastening technique. For example, theapparatus 10, or at least the receptacle's housing 30, 32, mayadditionally or alternatively be fastened to the user using a fasteningstrap and/or any other suitable fastening features.

The apparatus 10 may conform at least somewhat to the contours of theuser's body, and remain attached while allowing for at least somemovement of the user's body, because of the relatively flexible natureof the outer body of the housing 30, channel member 60 and adhesivemembrane 22, as well as the microneedle assembly 24 being movablymounted to the receptacle's housing 30, 32, such as by way of the spring46 and movably mounted sleeve 50. The movability of the microneedleassembly 24 relative to the receptacle's housing 30, 32 may becontrolled by the strength of the spring 46, the flexibility of theadhesive membrane 22 spanning between the attachment flange 38 and thechannel member 60, and the selective engagement between the upper edgeof the arresting flange 66 and the outer body 30.

Depending upon a variety of factors, the flexibility of one or more ofthe outer body 30, channel member 60 and adhesive membrane 22 may beadjusted or substantially eliminated. Similarly, the movability of themicroneedle assembly 24 relative to the receptacle's housing 30, 32 maybe adjusted or substantially eliminated, such by fixedly mounting thesleeve 50 to the receptacle's housing 30, 32 and eliminating the spring46.

Depending upon factors that may be associated with the stiffness of thespring 46, flexibility of the adhesive membrane 22, the size and numberof the microneedles 74 and how far they protrude outwardly through thecentral opening in the adhesive membrane 22, and/or the like, themicroneedles may penetrate the user's skin in response to the apparatus10 in its preactivated configuration being initially mounted to theuser's skin by way of the adhesive membrane 22. Alternatively oradditionally, the microneedles may penetrate or at least furtherpenetrate the user's skin in response subsequent pushing of theapparatus 10 against the user's skin, which may be facilitated bypushing the button disk 152, such as, but not limited to, prior toremoving the retention ring 12, or the like, from the apparatus 10. Forexample, the button disk 152 may be hit quickly with a hand or othersuitable object to force the microneedles 74 into the user's skin. Oncethe microneedles 74 extend sufficiently into the user's skin, therelatively deformable or flexible nature of each of the outer body ofthe housing 30, channel member 60 and adhesive membrane 22, as well asthe microneedle assembly 24 being movably mounted to the receptacle'shousing 30, 32, seek to allow the microneedles to sufficiently stay inthe user's skin, even while the user moves his or her body to areasonable extent.

At least partially reiterating from above and in accordance with oneaspect of this disclosure, the spring 46 is a force provider or may bepart of a force provider for forcing the microneedle assembly 24outwardly relative to the housing 30, 32 of the receptacle 14 in amanner that seeks to allow the microneedles 74 to extend a sufficientdistance outwardly from the receptacle subassembly 14 so that themicroneedles sufficiently enter and stay in the user's skin. While theapparatus 10, or at least the receptacle's housing 30, 32, is fastenedto the user as discussed above, the force provider that may comprise thespring 46 typically forces the microneedle assembly 24 outwardlyrelative to the receptacle's housing 30, 32 and against the skin of theuser in a manner that seeks to ensure that there is sufficiently goodcontact between the microneedle assembly and the skin during delivery ofthe drug formulation. The force provider that may comprise the spring 46seeks to ensure proper insertion of every microneedle of the microneedlearray 24 into the skin, and it further seeks to ensure that themicroneedles are maintained in the skin after insertion and until theapparatus 10 is removed following dosing. More generally, mechanicalfeature(s) comprising the spring 46, the deformable membrane 22 and/orother suitable features seek to ensure proper insertion of themicroneedles. The subject mechanical feature(s) may provide asubstantially uniform force between the microneedles and skin through aspring and joint combination with rotational and translational degreesof freedom. The degrees of freedom and force seek to ensure that themicroneedles and skin remain sufficiently engaged to one another duringmost body motions. The degrees of freedom also seek to prevent anydamage to the microneedles.

With the apparatus 10 fastened to the user and the microneedle assembly24 engaged against the skin of the user, the retention ring 12 or anyother suitable retention device may be removed, or at least partiallyremoved, from the remainder of the apparatus. The retention ring 12 maybe removed by manually pulling the retention ring off of the controller18. Then, the button disk 152 may be pressed with a sufficient amount offorce (e.g., a predetermined or more than a predetermined amount offorce) for transitioning the lower mechanical connector 56, 134 from itsconnected state to its disconnected state. This transition to thedisconnected state includes the protrusions proximate the tips of thelatch connector parts 56 being forced out of the lower groove connectorpart 134. Thereafter and in response to continued pressing of the buttondisk 152, relative movement occurs between the receptacle 14 andcartridge 16, which may again include the relative sliding between theprotruding tips of the latch connector parts 56 and the outer housing orflange 122 of the cartridge 16. In this regard, FIG. 16 schematicallyillustrates the apparatus 10 in an intermediate configuration betweenthe preactivated and activated configurations.

In response to further relative movement between the receptacle 14 andcartridge 16, which may be caused by pushing the button disk 152, theapparatus 10 reaches the activated configuration schematically shown inFIG. 17. As shown in FIG. 17, the cannula 92 has pierced the septum 108so that the cavities 98, 100 of the cartridge 16 are in fluidcommunication with the plenum chamber 90 (FIG. 6) of the receptacle 14.That is, as shown in FIG. 17, the reservoir or cartridge 16 is in aninner position and in fluid communication with the microneedle assembly24.

In the preactivated configuration shown in FIG. 15, the reservoir orcartridge 16 is in an outer position and out of fluid communication withthe microneedle assembly 24. In the illustrated embodiment, thereservoir or cartridge 16 is for being pushed by the pushbutton orcontroller housing 26 so that the cartridge moves along a path from theouter position (FIGS. 1 and 15) to the inner position (FIG. 17). In theinner position, the reservoir or cartridge 16 is in fluid communicationwith the microneedle assembly 24. The pushbutton or controller housing26 may be pushed at least farther into the housing 30, 32 of thereceptacle 14 for moving the reservoir or cartridge 16 along the pathfrom the first position to the second position. The pushbutton orcontroller housing 26 may be more generally referred to as a pushingmechanism. In this regard, the pushbutton or controller housing 26 maybe replaced with any other suitable pushing mechanism.

When the apparatus 10 reaches its activated configuration shown in FIG.17, the relative movement between the receptacle 14 and cartridge 16 maybe arrested in response engagement of at least one obstruction. Theobstruction may comprise at least one releasable mechanical connectionand/or at least one other engagement. For example, the lower cap 106 ofthe cartridge 16 may engage against an upper surface of the backingstructure 72 of the receptacle 14 to restrict relative movementtherebetween when the activated configuration is reached. Also, when theactivated configuration is reached, the protruding tips of the latchconnector parts 56 reach the upper groove connector part 132 (FIGS.8-10), so that the radially inwardly biased nature of the latchconnector parts cause the protrusions proximate the tips of the latchconnector parts 56 to protrude into the upper groove connector part 132,to engage at least one edge or shoulder of the cartridge 16 that atleast partially defines or is proximate the upper groove connector part132, to form mechanical connections that arrest the relative movementbetween the receptacle 14 and cartridge 16. In the first embodiment,these mechanical connections are snap-fit connections and they mayoptionally be substantially unreleasable connections. The mechanicalconnectors defined by the latch and upper groove connector parts 56, 132may be referred to as at least one detent or at least one uppermechanical connector 56, 132. Optionally, the upper mechanical connector56, 132 may be omitted.

In FIG. 18, some features, such as the button disk 152 of the controllerhousing 26 (FIG. 14), have been removed to clarify the view. As shown inFIG. 18, the latch 144 is automatically opened in response to thepushbutton or controller housing 26 being pushed sufficiently far intothe receptacle 14, and the pushing mechanism or plunger 140 is releasedin response to the latch being opened. More specifically and asschematically shown by large arrows in FIG. 18, in response to thepushbutton or controller housing 26 being sufficiently pushed so thatthe apparatus 10 reaches or substantially approaches the activatedconfiguration, the beveled surfaces 58, 170 (FIGS. 4, 5, 11, 12, 14 and17) of the sleeve 50 and latch 144 respectively engage one another. Inresponse to sliding engagement between the beveled surfaces 58, 170, theopposite actuating ends of the latch 144 are driven inwardly asschematically shown by large arrows in FIG. 18. As a result and asschematically shown by large arrows in FIG. 19, the latch 144 releasesthe plunger 140 and the spring 142 expands and, thus, forces the head164 of the plunger against the deformable membrane 116 of the cartridge16. More specifically, in response to the opposite ends of the latch 144being driven inwardly, the locking arms 174 bow outwardly and, thus,move out of the upper groove 166 in the shaft 162 of the plunger 140 sothat the latch 144 releases the plunger 140 and the spring 142 drivesthe plunger. In the first embodiment, the latching mechanism or latch144 is adapted to be transitioned between a latched state forrestricting expansion of the spring 142, and an unlatched state forallowing expansion of the spring 142; and the flexible membrane 22,which is connected between the microneedle assembly 24 and the housing30 of the receptacle subassembly 14 for both allowing and restrictingexpansion of the spring 142 independently of operation of the latch 144.

As best understood with reference to FIG. 20, which illustrates afully-activated or post-activated configuration of the apparatus 10, theguide disk 146 and associated features may function as a guide apparatusthat guides movement of the plunger 140 in a manner that seeks to ensurethat substantially all of the drug formulation is forced out of the widecavity 98 (FIGS. 10 and 16). The guide disk 146 may be sufficientlydeformable or flexible so that the inner edge of the guide disk remainswithin the lower groove 168 (FIG. 13) in the shaft 162 of the plunger140 while the plunger is moved by the spring 142 and the guide diskdeforms. A central portion of the guide disk 146 deforms into a roughlyconical shape (e.g., a substantially conical or substantiallyfrustoconical shape) so that the plunger 140 is driven into the widecavity 98 in a controlled manner. The guide disk 146 typically deformssuch that the inner circular periphery of the guide disk remains both inthe lower groove 168 and concentric with the outer circular periphery ofthe guide disk. This deformation and controlled movement of the guidedisk 146 seeks to keep the plunger 140 axis substantially parallel andcoincident with the axis of the wide cavity 98. In this way the plunger140 remains aligned with the wide cavity 98 and minimal, if any, fluidremains in the wide cavity 98 after the plunger has completed itsmotion. If there is any misalignment between the cartridge 16 andcontroller 18, the guide disk 146 seeks to allow for compensatingmovement of the plunger 140 in a manner that seeks to keep the plunger140 axis substantially parallel and coincident with the axis of the widecavity 98. The plunger 140 is movably mounted by way of the guide disk146 in a manner that seeks to eliminate frictional forces that wouldinhibit movement of the plunger.

At least partially reiterating from above and in accordance with oneaspect of this disclosure, the spring 142 is a force provider or may bepart of a force provider for forcing the plunger 140 against thedeformable membrane 116. This force provider may include at least thespring 142, one or more of the springs 142, and/or any other suitableforce providing features for flexing the deformable membrane 116, or thelike. Similarly, the plunger 140 may be more generally referred to as apushing mechanism, and the plunger may be replaced by or supplementedwith one or more other suitable pushing mechanisms.

The spring 142 drives the released plunger 140 against the reservoir orcartridge 16 for increasing the pressure of the fluid within thecartridge 16, so that the fluid is supplied from the cartridge to themicroneedle assembly 24. More specifically, the spring 142 drives thereleased plunger 140 against the reservoir or cartridge 16 for at leastpartially collapsing the reservoir or cartridge, so that the fluid issupplied to the microneedle assembly 24. More specifically and inaccordance with the first embodiment, the spring 142 drives the plunger140 so that its domed head 164 (FIG. 14) causes the deformable membrane116 to flex, and the domed head forces the deformable membrane 116 intocontact with substantially the entire surface of the cartridge's body 96that defines the wide cavity 98 (FIGS. 10 and 16), so that substantiallyall of the drug formulation in the wide cavity 98 flows into the narrowcavity 100. As indicated previously, the cartridge 16 comprises acontainer or reservoir, and the deformable membrane 116 being urged orforced into the wide cavity 98 may be characterized as the container orreservoir being at least partially collapsed.

The domed head 164 (FIG. 14) may be configured so that the contactbetween the deformable membrane 116 and wide cavity 98 (FIGS. 10 and 16)advances progressively from the widest area of the cavity 98 to thenarrowest area of the cavity 98 so that substantially all of the drugformulation may be forced out of the cavity 98. More specifically, thedomed head 164 and the substantially bowl-shaped wide cavity 98 may becooperatively configured, and the guide disk 146 may guide the plunger140, so that the contact between the deformable membrane 116 and widecavity 98 advances progressively from the widest area of the cavity 98to the narrowest area of the cavity 98, so that substantially all of thedrug formulation may be forced out of the cavity 98. As another specificexample, the curvature of the domed head 164 and the curvature of thebowl-shaped wide cavity 98 may be cooperatively selected in a mannerthat seeks to ensure that substantially all of the drug formulation isforced out of the cavity 98. Reiterating from above, the respective endof the passageway extending between the cavities 98, 100 may be openproximate, or more specifically at, the central portion of thesubstantially concave or substantially bowl-shaped wall that at leastpartially defines the wide cavity 98, and this configuration seeks toensure that substantially all of the drug formulation is forced out ofthe cavity 98. Alternatively, there may be some situations where it maynot be desirable for all of the drug formulation to be forced out of thecavity 98, or the like.

The drug formulation flows from the narrower cavity 100 through thecannula 92 into the plenum chamber 90 (FIG. 6). In the first embodiment,the drug formulation exits the plenum chamber 90 by flowing through therate control membrane and/or other suitable membrane on the top surface78 of the support plate 76 and then through the apertures in the supportplate to the channels associated with the microneedles 74, and then intothe user's skin. More generally, a force provider, which may comprisethe spring 142, at least indirectly forces the fluid to flow from thereservoir or cartridge 16 to the microneedle assembly 24 and then intothe skin of the user, and the flowpath(s) between the reservoir orcartridge and the user's skin may be provided or defined in any suitablemanner.

The drug formulation being forced out of the cavity 98 (FIGS. 10 and 16)as discussed above may comprise the drug formulation being pressurizedin a manner that causes the drug formulation to substantially uniformlyfill the plenum chamber 90, and flow through the rate control membraneand/or other suitable membrane on the top surface 78 of the supportplate 76 to each of the microneedles 74. The rate control membraneand/or other suitable membrane on the top surface 78 of the supportplate 76 may be selected so that the pressure drop resulting from thedrug formulation flowing through the rate control membrane and/or othersuitable membrane substantially consumes all of the pressure energyimparted into the drug formulation through the action of the plunger140. As a result, there may be only capillary flow of the drugformulation through the microneedle assembly 24. In addition oralternatively, forced flow of the drug formulation through themicroneedle assembly 24 may be caused by the pressure energy impartedinto the drug formulation through the action of the plunger 140.

In one aspect of this disclosure, the delivery the drug formulation bythe apparatus 10 may be by way of pressure driven flow and capillaryflow. When the microneedles of the microneedle assembly 24 are isinserted into the skin and the apparatus 10 is in it actuated state, themicroneedles may be wetted from interstitial fluid, and the drugsolution may flow from the reservoir or cartridge 16 under pressure. Thetwo liquid fronts may meet in or proximate the apertures defined in thesupport plate 76, and then the drug formulation may flow freely into theskin. When the reservoir or cartridge 16 is emptied, capillary forcesmay draw at least some of, or substantially all of, the remaining drugformulation out of the apparatus 10 and into the skin.

In one aspect of this disclosure, the pushbutton or controller housing26 may be referred to as an outer pushing mechanism, and the plunger 140may be referred to as an inner pushing mechanism that is mounted to theouter pushing mechanism for being moved relative to the outer pushingmechanism for at least partially collapsing the reservoir or cartridge16 in response to predetermined relative movement between the outerpushing mechanism and the housing 30, 32 of the receptacle 14. At theoccurrence of the predetermined relative movement between the housing30, 32 and the outer pushing mechanism or controller housing 26, thebeveled surfaces 58, 170 (FIGS. 4, 5, 11, 12, 14 and 17) of the sleeve50 and latch 144 respectively engage one another as discussed above, orthe latch 144 may be opened in any other suitable manner.

In one example, the plunger 140 and deformable membrane 116 may beconstructed of materials that are more deformable or flexible, and lessrigid, than the material of the cartridge's body 96, for helping tofacilitate substantially all of the drug formulation being forced out ofthe wide cavity 98 (FIGS. 10 and 16). For example and further regardingthe movable member that may more specifically be in the form of thedisk-shaped deformable membrane 116, this deformable membrane may beformed from any suitably configured material that may be extensible,flexible, foldable, stretchable and/or the like. As a more specificexample, the deformable membrane 116 may be a flexible non-porous film,such as polyisoprene film. In one example, the deformable membrane 116may have very low fluid/vapor permeability and a low tensile modulus.For example, the water vapor transmission of the deformable membrane 116would be low when used with water-based drug formulations. The tensilemodulus of the deformable membrane 116 may be less than about 1.5 GPa,or more specifically less than 1.5 GPa. The low tensile modulus seeks tominimize the force required to fully deploy the plunger 140.Alternatively, the deformable membrane 116 may have a higher tensilemodulus, and a stronger spring 142 may be used. Suitable film laminatesmay be used as the deformable membrane 116.

In the first embodiment of this disclosure, the deformable membrane 116stretches to conform (e.g., substantially confirm) to the shape of thewide cavity 98 (FIGS. 10 and 16). In addition or alternatively, thedeformable membrane 116 may be configured for at least partiallyunfolding in a manner such that the deformable membrane substantiallyconforms to the shape of the wide cavity 98. As a more specific exampleof an alternative embodiment, the deformable membrane 116 may be in theform of, substantially similar to, or at least partially in the form ofa bellows, or the like, that unfolds to substantially conform to theshape of the wide cavity 98. In this alternative embodiment, thedeformable membrane 116 may not stretch, such that the deformablemembrane 116 may be made from a non-extensible material. In anotheralternative embodiment, when a cavity at least partially defined by thedeformable membrane 116 is filled the deformable membrane inflatesoutwardly relative to a flat base, and the head of the plunger 140 maybe flat for flattening the inflated deformable membrane against the flatbase. In another alternative embodiment, the cartridge 16 may be in theform of a deformable member such as a bag or bladder that is supportedby a flat support surface, and the head of the plunger 140 may be flatfor flattening the cartridge against the flat support surface.

More generally regarding materials from which the apparatus 10 may beconstructed, suitable materials may be selected from those typicallyused for medical devices, such as medical devices for containing anddispensing drug formulations. As more specific examples, the springs 46,142, frame or bezel 70 and cannula 92 may be constructed of metal, suchas stainless steel or any other suitable material. Other components ofthe apparatus 10 may be constructed from polymeric (e.g., plastic)materials. For example, the relatively flexible outer body 30 andchannel member 60 of the receptacle 14 may be constructed of a naturalrubber material. As a further example, the self-sealing septum 108 maycomprise silicone and/or any other suitable materials. The body 96 ofthe reservoir or cartridge 16 may made of a rigid polymeric materialsuch as, but not limited to, cyclic olefin polymer, and the cartridgemay be sealed with polyisoprene or another suitable material. All of thevarious materials from which the apparatus 10 is constructed may bebiocompatible and meet U.S. Pharmacopeial Convention requirements.

As mentioned above, the springs 46, 142 of the first embodiment may havedifferent sizes and/or strengths as compared to one another. The spring46 may be configured so that, while the apparatus 10 is fastened to auser as discussed above, the spring 46 forces the microneedle assembly24 against the user's skin with a force in a range of 1 N to 10 N, ormore generally in a range of about 1 N to about 10 N, or any othersubranges therebetween. The force provided by the spring 142 may depend,for example, on the size of the microneedle assembly 24, the ratecontrol membrane and/or other suitable membrane that may be positionedat the top surface 78 of the microneedle assembly 24, and the desiredflow rate. The force provided by the spring 142 may be in a range of 1.1N to 1.3 N, about 1.1 N to about 1.3 N, 2 N to 2.2 N, about 2 N to about2.2 N, 2.4 N to 2.6 N, about 2.4 N to about 2.6 N, 2.7 N to 2.9 N, about2.7 N to about 2.9 N or any other subranges therebetween.

More generally and reiterating from above, each of the springs 46, 142may be more generally referred to as a force provider and/or may bereplaced or supplemented with one or more suitable force providers. Insuch alternative embodiments, suitable force providers may include, butare not limited to, compressed foams, swellable polymers, pneumaticactuators, hydraulic actuators, electrical solenoid actuators,piezoelectric actuators, electrochemical actuators, rotary mechanicalactuators and/or the like.

Referring to FIGS. 21-23, a second embodiment of this disclosure is likethe first embodiment, except for variations noted and variations thatwill be apparent to those of ordinary skill in the art. For example, thesecond embodiment may be referred to as a second version or othermodification of the first embodiment, or the like. Accordingly, thereference numerals used above are also used in the following discussionof the embodiment, or the like, illustrated in FIGS. 21-23.

FIGS. 21 and 22 are isolated pictorial views of the inner or lowersupport structure 52 (e.g., see FIGS. 5 and 6), in accordance with thesecond embodiment, or the like. The lower support structure 52 may be inthe form of a unity body having a base plate 200 with a centrallylocated, downwardly extending, tiered backing structure 72. As shown inFIG. 22, the backing structure 72 may include a central partition 202that is offset from the remainder of the base plate 200. The lowersurface of the partition 202 defines a side of the plenum chamber 90(FIGS. 6, 23 and 24), and the supply passageway 91 for at leastpartially receiving the cannula 92 (FIGS. 5, 23 and 24) extends throughthe partition 202. Referring to FIG. 22, each edge, or the like, of thepartition 202 may be offset from the remainder of the base plate 200 byway of at least one step or shoulder 204 positioned between inner andouter risers 206, 208.

As shown in FIG. 22, an annular peripheral flange 209 may extenddownwardly from the periphery of the base plate 200, so that theperipheral flange extends at least partially around each of the backingstructure 72 and the annular inner and outer channels 84, 86 of thesupport structure 52. The annular inner channel 84 may be at leastpartially defined between the shoulders 204 and inner risers 206. Theannular outer channel 86 may be at least partially defined between theouter risers 208 and the flange 209.

As best understood with reference to FIG. 21, the lower supportstructure 52 may include one or more arresting lobes 66 that comprisetruncated, chamfered or rounded corners of the base plate 200 andassociated portions of the flange 209. In addition, the lower supportstructure 52 may include an annular, upwardly facing lower seat 54 forthe spring 46 (FIGS. 5 and 23). Also, a cylindrical guide sleeve 212,and a receptacle 214 for the sealing gasket 94 (FIGS. 5 and 24), mayextend upwardly from the central partition 202 of the backing structure72.

Referring also to FIGS. 23 and 24, the gasket 88 may be engaged in oneor both of the inner and outer channels 84, 86, so that the gasket 88 isengaged securely against the margin of the rate control membrane and/orother suitable membrane that forms or is positioned at the top surface78 of the microneedle assembly 24. These secure engagements associatedwith the gasket 88 may result at least partially from the frame 70 beingfixedly mounted to the backing structure 72, or more specifically frame70 being fixedly mounted between the peripheral channel 82 of themicroneedle assembly 24 and the outer channel 86 of the backingstructure 72. The frame 70 may be mounted between the peripheral andouter channels 82, 86 in any suitable manner. For example, at least onemounting member that may be in the form of an annular frame member 216may be positioned in the outer channel 86 and fixedly mounted to thelower surface of the base plate 200, such as by adhesive material,ultrasonic welding, mechanical fasteners and/or in any other suitablemanner, wherein the outer marginal portion of the frame 70 is fixedlysecured between the inner marginal portion of the frame member 216 andthe lower surface of the base plate 200.

As best understood with reference to FIGS. 21 and 23, the upper andlower support structures 50, 52 may be fixedly connected to one anotherby one or more snap-fit connections, wherein each snap-fit connectionmay comprise one or more flexible, resilient tabs or latches 218 (FIG.23) of the upper support structure that respectively extend through andare fixedly associated with holes or slots 210 of the lower supportstructure. More specifically, during relative movement between the upperand lower support structures 50, 52 that may be associated with assemblyof the receptacle 14, the free ends of the latches 218 of the uppersupport 50 may pass through the holes 210 of the lower support structure52, and the radially inwardly biased nature of the upper support's latchconnector parts 218 may cause the protrusions proximate the tips of theupper support's latch connector parts 218 to engage at least one edge orshoulder of the lower support structure 52 that optionally at leastpartially defines or is proximate the holes 210 of the lower supportstructure 52, to form mechanical connections that substantially fixedlyconnect the upper and lower support structures 50, 52 to one another.

Similarly and referring to FIG. 23, the cartridge and controllersubassemblies 16, 18 may be fixedly connected to one another by one ormore snap-fit connections, wherein each snap-fit connection may compriseone or more flexible, resilient tabs or latches 218 of the controllersubassembly 18 that respectively extend through and are fixedlyassociated with holes or slots 210 in the wide closure 102 of thecartridge subassembly 16. More specifically, during relative movementbetween the cartridge and controller subassemblies 16, 18 that may beassociated with assembly of the apparatus 10, the free ends of thelatches 218 of the controller subassembly 18 may pass through the holes210 of the cartridge subassembly 16, and the radially inwardly biasednature of the controller subassembly's latch connector parts 218 maycause the protrusions proximate the tips of the controller subassembly'slatch connector parts 218 to engage at least one edge or shoulder of thecartridge subassembly 16 that optionally at least partially defines oris proximate the holes 210 of the cartridge subassembly 16, to formmechanical connections that substantially fixedly connect the cartridgeand controller subassemblies 16, 18 to one another. At least partiallyreiterating from the foregoing, the controller subassembly 18 mayinclude at least one flexible, resilient latch 218 extending outwardlyrelative to the controller subassembly's frame or housing 26 forconnecting the controller subassembly to the cartridge subassembly 16.

Throughout this disclosure, the positions of the latches 56, 218 and theedges or shoulders for respectively engaging the protrusions proximatethe free ends of the latches may be interchanged with one another,and/or the snap-fit connections may be supplemented with or replaced byone or more other suitable connections. For example and at leastpartially reiterating from the foregoing, the controller subassembly 18may include at least one flexible, resilient latch 218 extendingoutwardly relative to the controller subassembly's frame or housing 26for connecting the controller subassembly to the cartridge subassembly16 and/or the receptacle subassembly 14; and/or, even though not shownin the drawings, the cartridge subassembly 16 may include at least oneflexible, resilient latch 218 extending outwardly relative to thecartridge subassembly's frame, housing, or the like, for connecting thecartridge subassembly to the controller subassembly and/or thereceptacle subassembly 14, or the like.

As at least partially shown in the drawings, the latches 56, 218 and theedges or shoulders for respectively engaging the protrusions proximatethe free ends of the latches may be respectively arranged insubstantially coaxially arranged in series that are spaced apart alongthe axis of the apparatus 10. That is, the snap-fit connector parts(e.g., the latches 56, 218 and corresponding connector parts 132, 134,210) may be respectively arranged in substantially coaxially arrangedseries that are spaced apart along the axis of the apparatus 10.

Referring to FIG. 23, elongate channels 222 that extend outwardly fromthe narrow cavity 100 and are open to the wide cavity 98 (FIGS. 10 and16) may be included in the surface of the cartridge's body 96 thatdefines the wide cavity 98. When the apparatus 10 is operated asdiscussed above so that the plunger 140 causes the deformable membrane116 to flex into contact with substantially the entire surface of thecartridge's body 96 that defines the wide cavity 98, the channels 222may be operative in a manner that seeks to ensure that substantially allof the drug formulation in the wide cavity 98 flows into the narrowcavity 100.

As best understood with reference to FIGS. 21-23, the lobes arrestinglobes 66 may be arranged in a series that extends around the microneedleassembly 24. Referring to FIG. 23, also when the apparatus 10 is beingused as discussed above, the arresting lobes 66, or the like, maytemporarily engage the inner surface of the sidewall 34 of the outerbody 30 in response to predetermined compression of the outer spring 46.This engagement can be for restricting the microneedle assembly 24 frombeing pushed too far into the interior of the receptacle subassembly 14.More specifically, this engagement can be for temporarily restrictingfurther relative movement in one direction between the compound housing30, 32 and the upper support structure 50 in a manner that seeks toprevent the microneedles 74 from becoming recessed into the receptacle14 in a manner that may prevent the microneedles from being sufficientlyinserted into a user's skin. That is, when (e.g., if) the outer spring46 is sufficiently compressed during use, the arresting lobes 66 maytemporarily engage the inner surface of the sidewall 34 of the outerbody 30 for restricting further relative movement in one directionbetween the compound housing 30, 32 and the upper support structure 50so that the microneedles 74 remain positioned sufficiently outwardlyfrom the housing of the receptacle 14, so that the microneedles remainsufficiently exposed for extending into a user's skin.

In accordance with one aspect of this disclosure, a least one arrestingmember may comprise the arresting flange or lobes 66, wherein the aleast one arresting member may be positioned between the microneedleassembly 24 and a housing of the apparatus, such as the housing 30, 32of the receptacle 14. The at least one arresting member, arrestingflange or lobes 66 may be configured for restricting any movement of themicroneedles 74, or at least tips of the microneedles, into an interiorof the housing of the receptacle. More specifically, the at least onearresting member, arresting flange or lobes 66 may be connected to andextend outwardly from the microneedle assembly 24 for engaging aninterior surface of the housing 30, 32 of the receptacle 14 forrestricting any movement of the microneedles 74, or at least tips of themicroneedles, into an interior of the housing of the receptacle.

Referring to FIGS. 23 and 23, also when the apparatus 10 is being usedas discussed above, the lower or narrow closure 104, or the like, of thecartridge subassembly 16 may move into the guide sleeve 212, whereinsliding, guiding relative movement between the cartridge subassembly 16and guide sleeve 212 seeks to ensure substantially coaxial insertion ofthe cannula 92 into the cartridge subassembly.

The above examples are in no way intended to limit the scope of thepresent invention. It will be understood by those skilled in the artthat while the present disclosure has been discussed above withreference to exemplary embodiments, various additions, modifications andchanges can be made thereto without departing from the spirit and scopeof the inventions, some aspects of which are set forth in the followingclaims.

What is claimed is:
 1. A transdermal drug delivery apparatus comprising:a receptacle comprising a housing and a microneedle assembly mounted tothe housing; a reservoir for being mounted to the receptacle, thereservoir having an interior for containing fluid for being supplied tothe microneedle assembly, wherein the apparatus is adapted so that, whenthe apparatus is assembled, the reservoir is configured to move relativeto the microneedle assembly along a path from an outer position to aninner position, the reservoir being closer to the microneedle assemblyin the inner position than in the outer position, in the outer position,the reservoir being out of fluid communication with the microneedleassembly, and in the inner position, the reservoir being in fluidcommunication with the microneedle assembly; and a plurality ofconnector parts spaced apart from one another along the path, andconfigured for releasably securing the reservoir in a first position,and securing the reservoir in a second position.
 2. The apparatusaccording to claim 1, wherein the plurality of connector parts comprisesnap-fit connector parts.
 3. The apparatus according to claim 1, furthercomprising a pushing mechanism for moving the reservoir from the outerposition to the inner position.
 4. The apparatus according to claim 3,wherein the pushing mechanism comprises a pushbutton.
 5. The apparatusaccording to claim 3, wherein the pushing mechanism is an outer pushingmechanism, and the apparatus further comprises: an inner pushingmechanism mounted to the outer pushing mechanism for being movedrelative to the outer pushing mechanism; and a force provideroperatively associated with the inner pushing mechanism for moving theinner pushing mechanism relative to both the outer pushing mechanism andthe reservoir for at least partially collapsing the reservoir.
 6. Theapparatus according to claim 5, wherein the apparatus further comprisesa latching mechanism for releasing the inner pushing mechanism inresponse to predetermined relative movement between the outer pushingmechanism and the housing.
 7. A method of at least partially using atransdermal drug delivery apparatus, the method comprising: fasteningthe transdermal drug delivery apparatus to a user; engaging amicroneedle assembly of the apparatus against skin of the user so that afirst force provider of the apparatus forces the microneedle assemblyagainst the skin; and while the apparatus is fastened to the user andthe first force provider is forcing the microneedle assembly against theskin, causing a second force provider of the apparatus to at leastindirectly force fluid to flow from a reservoir of the apparatus to themicroneedle assembly.
 8. The method according to claim 7, wherein theengaging of the microneedle assembly of the apparatus against the skinis comprised of compressing the first force provider.
 9. The methodaccording to claim 7, wherein the engaging of the microneedle assemblyagainst the skin occurs prior to the fastening of the apparatus to theuser.
 10. The method according to claim 7, further comprising moving thereservoir into fluid communication with the microneedle assembly,wherein the causing of the second force provider to at least indirectlyforce the fluid to flow is at least partially responsive to the movingof the reservoir into fluid communication with the microneedle assembly.11. The method according to claim 7, wherein: the first force providercomprises at least one spring; and the first force provider forcing themicroneedle assembly against the skin is comprised of the at least onespring being compressed and forcing the microneedle assembly against theskin.
 12. The method according to claim 11, wherein: the second forceprovider comprises a second spring; and the causing of the second forceprovider of the apparatus to at least indirectly force the fluid to flowis comprised of the second spring expanding.
 13. The method according toclaim 7, wherein the causing of the second force provider of theapparatus to at least indirectly force the fluid to flow from thereservoir is comprised of pushing a pushbutton of the apparatus.
 14. Themethod according to claim 13, wherein the pushing of the pushbuttonmoves the reservoir into fluid communication with the microneedleassembly.
 15. The method according to claim 7, wherein the second forceprovider at least indirectly forcing fluid to flow from the reservoir iscomprised of the reservoir being at least partially collapsed.
 16. Themethod according to claim 15, wherein the second force provider at leastindirectly forcing fluid to flow from the reservoir is comprised offorce from at least one expanding spring urging a pushing mechanismagainst the reservoir.
 17. A method of using a transdermal drug deliveryapparatus, the method comprising: engaging a microneedle assembly of theapparatus against skin of a user, comprising causing relative movementbetween a housing of the apparatus and the user; and then moving areservoir of the apparatus into fluid communication with the microneedleassembly, comprising moving the reservoir relative to both the housingand the microneedle assembly, wherein the moving of the reservoir iscomprised of pushing a portion of the apparatus that is for moving thereservoir, the pushing of the portion is comprised of pushing theportion with sufficient force so that at least one connector of theapparatus at least partially releases the portion from the housing inresponse to the pushing, and the moving of the reservoir is responsiveto the at least one connector of the apparatus at least partiallyreleasing the portion from the housing.
 18. The method according toclaim 17, wherein the portion of the apparatus comprises a pushbutton.19. The method according to claim 17, wherein the at least one connectoris a snap-fit connector.
 20. The method according to claim 17, wherein:the at least one connector is at least one first connector thatcomprises a connector part; the method further comprises the moving ofthe reservoir being arrested by at least one second connector of theapparatus transitioning from an unconnecting state to a connectingstate; and the at least one second connector also comprises theconnector part.